Inhaled Insulin for Diabetes Mellitus

Tarun K. Mandal

Disclosures

Am J Health Syst Pharm. 2005;62(13):1359-1364. 

In This Article

Factors Affecting the Pulmonary Delivery of Insulin

During breathing, drug particles pass, along with air, from the upper airways (oropharynx and larynx) to the lower airways. The lower airways start in the trachea and are followed by successive bifurcations into bronchi and bronchioles within the lungs. Down to this point, the spaces are called conductive airways. The terminal bronchioles then divide into respiratory bronchioles until the ultimate respiratory zone, the alveoli, are reached. Drug particles enter the lungs by trancytosis. The rate of drug absorption is expected to vary at different sites within the lungs due to the variable thickness of the mucosal surface.[7] There is a steep increase in the surface area of the lungs within the alveolar region, which is the target site for drug deposition when systemic drug absorption is desired.

A major challenge of pulmonary drug delivery is the lack of reproducibility in the deposition site of the administered dose.[8] A wide range of factors, including the mode of inhalation and aerosol properties, influence the deposition of drugs within the respiratory tract. The most important features of inhalation affecting drug deposition are inhaled volume, flow rate, and any breathholding pause maintained at the end of inspiration. The greater the inhaled volume, the more peripherally the particles will be distributed into the lungs. By contrast, as the inhaled flow rate is increased, particles are more likely to be deposited in the oropharynx or in the large central airways of the lungs by inertial impaction. A period of breath-holding enhances deposition in the more peripheral parts of the lungs by gravitational sedimentation.

The vital physical property of the aerosol is the size of the particles. As the particle size increases from about 2 μm, deposition in the oropharynx and large conducting airways becomes more likely; although less aerosol is exhaled, less reaches the most peripheral parts of the lungs. The ideal size for pulmonary delivery of particles into the deep lung region is between 1 and 5 μm in geometric diameter, assuming the density of the particle is 1 g/cm3. However, aerodynamic diameter rather than geometric diameter controls particle deposition in the lungs. Aerodynamic diameter is a product of geometric diameter and the square root of density. When a particle becomes more porous, it becomes lighter in density, and the overall aerodynamic diameter decreases. Thus, as particle density decreases, particles that are larger in geometric diameter can deposit into the deep lung region. Throughout this article, particle size and particle diameter represent geometric diameter, unless stated otherwise.

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